fondaparinux and Kidney-Diseases

Chronic kidney disease (CKD) is prevalent and affects an ever-increasing proportion of patients presenting with acute coronary syndrome (ACS). Patients with CKD have a higher risk of ACS and significantly higher mortality, and are also predisposed to increased bleeding complications. Antiplatelet and antithrombotic drugs form the bedrock of management of patients with ACS. Most randomized trials of these drugs exclude patients with CKD, and current guidelines for management of these patients are largely based on these trials. We aim to review the safety and efficacy of these drugs in patients with CKD presenting with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Chronic Disease; Clinical Trials as Topic; Clopidogrel; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine; Uremia

The study aim was to determine the value of fondaparinux at the once-daily 1.5 mg dose in patients with moderate renal impairment (creatinine clearance between 20 and 50 ml/min). Pharmacokinetic simulations were performed using a population pharmacokinetic model based on data obtained in 756 patients undergoing major orthopedic surgery. The efficacy (venous thromboembolism) and safety (major bleeding) of 1.5 mg fondaparinux were determined by analyzing the available data obtained in all thromboprophylaxis trials using this dosage. The predicted steady-state exposure [area under the plasma concentration-time curve from 0 to 24 h (AUC0-24)] to fondaparinux between patients with moderate renal impairment receiving 1.5 mg and patients with normal renal function receiving 2.5 mg was similar. In four phase II trials (two trials versus placebo, one versus enoxaparin and one without comparator), 353 patients undergoing total hip or knee replacement (10.8% with moderate renal impairment) received fondaparinux 1.5 mg. The overall rate of venous thromboembolism and major bleeding was 10.4 and 0.3%. Fondaparinux 1.5 mg was significantly more effective than placebo (P < 0.01) and was as effective as, and tended to be safer (P = 0.05) than, twice-daily 30 mg enoxaparin. The effect was maintained in patients with moderate renal impairment. The once-daily administration of 1.5 mg fondaparinux in patients with moderate renal impairment resulted in a predicted exposure to the drug similar to that achieved with 2.5 mg in patients with normal renal function. This dosage regimen showed a favorable efficacy/safety clinical profile and should be appropriate in preventing venous thromboembolism in patients with moderate renal impairment.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Fondaparinux; Humans; Kidney Diseases; Male; Middle Aged; Polysaccharides; Venous Thromboembolism

Fondaparinux was associated with reduced major bleeding events and improved survival compared with low-molecular-weight heparin (LMWH) in a large randomized clinical trial involving patients with non-ST-segment elevation myocardial infarction (NSTEMI). Large-scale experience of the use of fondaparinux vs LMWH in a nontrial setting is lacking.. To study the association between the use of fondaparinux vs LMWH and outcomes in patients with NSTEMI in Sweden.. Prospective multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry involving 40,616 consecutive patients with NSTEMI who received fondaparinux or LMWH between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010.. In-hospital treatment with fondaparinux or LMWH during the hospital stay.. In-hospital severe bleeding events and death and 30- and 180-day death, MI, stroke, and major bleeding events. Logistic regression models adjusted for calendar time, admitting hospital, baseline characteristics, and in-hospital revascularization.. In total, 14,791 patients (36.4%) were treated with fondaparinux and 25,825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42-0.70). A total of 394 patients (2.7%) in the fondaparinux group died while in the hospital vs 1022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63-0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups.. In routine clinical care of patients with NSTEMI, fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.

Topics: Aged; Cardiovascular Diseases; Cohort Studies; Electrocardiography; Female; Fondaparinux; Glomerular Filtration Rate; Hemorrhage; Heparin, Low-Molecular-Weight; Hospital Mortality; Humans; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Polysaccharides; Registries; Sweden

Topics: Anticoagulants; Fondaparinux; Glomerular Filtration Rate; Hematoma; Humans; Kidney Diseases; Male; Middle Aged; Polysaccharides; Venous Thrombosis

To illustrate clinical and management issues in the prevention of venous thromboembolism (VTE) in health systems.. Lack of evidence to guide the choice among available anticoagulants and the dosing, timing of initiation, and duration of therapy for VTE prevention in certain clinical situations can present challenges for clinicians. Patient characteristics such as the presence of obesity, epidural catheters, renal impairment, or heparin- induced thrombocytopenia complicate the decision-making process. The introduction of new anticoagulants may overcome some of the clinical challenges associated with VTE prophylaxis, but determining whether to add new agents to the formulary and restrict their use may pose management challenges. The safety, effectiveness, ease of use, and cost of new agents compared with older agents already on the formulary are primary considerations.. An understanding of the clinical and management issues involved in preventing VTE is needed to improve the use of anticoagulants and reduce the incidence of VTE in health systems.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Bariatric Surgery; Colonic Neoplasms; Dalteparin; Female; Fondaparinux; Heart Failure; Humans; Kidney Diseases; Male; Middle Aged; Obesity; Perioperative Care; Pharmacy Service, Hospital; Polysaccharides; Venous Thromboembolism

To study the effect of fondaparinux, a new antithrombotic agent, as an anticoagulant during a 4-hour conventional hemodialysis session. materials and methods: Fondaparinux was administered as an anticoagulant to 16 chronic hemodialysis patients during a single 4-hour hemodialysis session at an intravenous bolus dose of 2.5 mg. Eight patients were using high-flux polyester polymer alloy (PEPA) dialyzers (Group A) and the remainder low-flux polysulfone dialyzers (Group B), whilst all had received conventional doses of tinzaparin sodium as an anticoagulant during the previous month. The dialyzers were primed with 1 l of normal saline containing 5,000 IU of unfractionated heparin. Blood samples for the measurement of INR, APTT (activated partial thromboplastin time) and anti-Xa levels were taken before the study dialysis session (pre), 5 min postdialysis (post), and before the next dialysis session (next). Mean fibrin/clot formation in the extracorporeal circuit and dialyzer was assessed macroscopically by visual inspection and was graded using a 4-point scale.. Predialysis anti-Xa levels were 0.04 A+/- 0.03 IU/ml in Group A, and 0.025 A+/- 0.025 IU/ml in Group B (p = NS). Postdialysis anti-Xa levels were significantly higher than predialysis levels in both groups (Group A = 0.16 A+/- 0.04 IU/ml, Group B = 0.46 A+/- 0.12 IU/ml, p < 0.02 for both) and significantly higher in Group B compared to Group A (p < 0.025). Anti-Xa levels before the next dialysis session were 0.06 A+/- 0.04 IU/ml in Group A and 0.25 A+/- 0.06 IU/ml in Group B (p < 0.0001 between Groups A and B). APTT values were significantly higher in postdialysis than predialysis samples for both groups (higher by 27.0 A+/- 26.0% in Group A and 24.3 A+/- 31.9% in Group B). No significant differences were found when comparing APTT values in pre, post and next samples between Groups A and B. No differences were also found between pre, post and next samples for INR values, either within or between groups. Mean fibrin/ clot formation score in the extracorporeal circuit at the end of the study dialysis session was significantly higher in patients of Group A than those of Group B (p < 0.05). Dialysis had to be terminated before the completion of 4 hours in 2 patients of Group A because of the presence of extensive fibrin/clots in the circuit and dialyzer.. Our findings indicate that fondaparinux sodium at an intravenous dose of 2.5 mg can be used successfully as an anticoagulant during a 4-hour conventional hemodialysis session in patients dialyzed with low-flux polysulfone dialyzers, but not in those dialyzed with high-flux dialyzers. However, anti-Xa levels in the former patients were still increased before the next dialysis session, potentially exposing the patients to an increased risk of bleeding.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Chronic Disease; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Injections, Intravenous; International Normalized Ratio; Kidney Diseases; Male; Middle Aged; Partial Thromboplastin Time; Polysaccharides; Renal Dialysis